Viral Pathogenesis 2

Question 1

What happens in the innate immune system when a virus infects a cell?

Answer 1

The virus infected cell will produce IFN-alpha/beta. The virus will also interact with macrophages and dendritic cells. The macrophages and dendritic cells will produce IFN-alpha/beta, IL-12 and pro-inflammatory cytokines (IL-1, IL-6, TNFalpha) and chemokines. The IFN-alpha/beta and the IL-12 activate NK cells. The NK cells will produce IFN-gamma and also kill infected cells. Dendritic cells will present the antigen to T cells.

Question 2

What are the roles of the type 1 interferons (IFN-alpha/beta)?

Answer 2

Inhibit viral replication, activate NK cells, enhance MHC class I expression

Question 3

What are the roles of type 2 interferons (IFN-gamma)

Answer 3

Inhibit viral replication, activates macrophages, enhances MHC class I and class II expression

Question 4

What are the two ways that viruses can combat the immune system?

Answer 4

Either by not being recognised by the immune system or by interfering with the function of a particular part of the immune system

Question 5

What is antigenic drift?

Answer 5

Change in the antigenic structure of a virus

Question 6

What viruses undergo antigenic drift?

Answer 6

HIV and influenza

Question 7

How does vaccinia virus inhibit T cell priming by DC?

Answer 7

By encoding a homologue of the cytoplasmic tail of TLR4 - this means that the signalling molecules will bind to the homologue rather than the actual cytoplasmic tail of TLR4 and signalling will be inhibited.

Question 8

How does the HSV virus inhibit T cell priming by DC?

Answer 8

By blocking the signal transduction from the TLR

Question 9

How do vaccinia and HCV viruses inhibit T cell priming by DC?

Answer 9

By inhibiting the maturation of DCs by blocking the cytokines released by immature DCs to signal to other DCs to mature

Question 10

How do measles and CMV viruses inhibit T cell priming by DC?

Answer 10

By interfering with the costimulatory molecules of DCs required for T cell priming

Question 11

How does HIV evade CD8 T cell recognition?

Answer 11

By mutating the epitope so can’t associate with MHC class I and so the TCR won’t recognise them. Also by encoding a protein which induces endocytosis of MHC class I

Question 12

How does HSV evade CD8 T cell recognition?

Answer 12

By encoding a peptide that blocks the TAP transporter from the cytosolic side

Question 13

How does CMV evade CD8 T cell recognition?

Answer 13

By encoding a peptide that blocks the TAP transporter from the luminal side

Question 14

How does adenovirus evade CD8 T cell recognition?

Answer 14

By encoding a protein that binds to MHC in the ER and won’t let it get out into the vesicle

Question 15

How does EBV evade CD8 T cell recognition?

Answer 15

By inhibiting the proteosome complex which degrades the viral proteins into epitopes

Question 16

Which viruses decrease production of MHC class I genes?

Answer 16

HIV, RSV, adenovirus

Question 17

What viruses are humans with an NK cell defiency highly susceptible to?

Answer 17

varicella and cytomegalyvirus

Question 18

What two kinds of receptors do NK cells have?

Answer 18

Activation receptors which recognise things on the infected cell surface which are there as a result of viral infections, and inhibitory receptors which recognise MHC class I molecules.

Question 19

When will the NK cell be able to kill the target cell?

Answer 19

If the activation receptor is activated and if MHC class I is aberrantly expressed or not expressed at all so the inhibitory receptor is not activated

Question 20

What is the purpose of this?

Answer 20

So that if the virus makes the cell stop expressing MHC class I to evade CD8 T cells then NK cells can kill them

Question 21

How does human CMV evade NK cell killing?

Answer 21

By encoding an MHC class I like molecule that is expressed on the cell surface that delivers a negative signal to NK cells but cannot present proteins to CD8 T cells

Question 22

What is the role of interferons?

Answer 22

Helps neighbouring cells not to get infected by the virus - binding of interferons to receptors stimulates a signalling pathway that leads to up regulation of proteins such as MHC class I and class II and PKR

Question 23

What happens in the PKR pathway?

Answer 23

Interferon binds, synthesis of PKR in an inactive form, PKR is autophosprylated in the presence of dsRNA as a cofactor, active PKR phoshprylates eIF2alpha to its inactive form to prevent translation of proteins from the ribosome

Question 24

How does dsRNA act as a cofactor?

Answer 24

PKR hooks over the dsRNA to bring the two domains in close proximity so they can autophosphorylate

Question 25

How does EBV and adenovirus evade the PKR pathway?

Answer 25

Their RNA is only in short stretches - not long enough for the PKR to bind

Question 26

How do vaccinia and reovirus evade the PKR pathway?

Answer 26

By encoding proteins which bind to their dsRNA to protect it

Question 27

How else does vaccinia evade the PKR pathway?

Answer 27

By encoding a homologue of eIF2 so that if PKR is activated it will phosphorylate the homologue rather than the real eIF2

Question 28

What are some genetic factors that influence susceptibility to viral infection?

Answer 28

Inherited defects e.g. lack of Ig class, polymorphisms e.g. in the MHC genes, defects in interferon inducible genes, defects in expressing receptors

Question 29

What deficiency may be beneficial in avoiding HIV?

Answer 29

Lack of CCR5 gene

Question 30

What are some non genetic factors that influence susceptibility to viral infection?

Answer 30

Age (newborns and the elderly), malnutrition, hormones, pregnancy, dual infections

Question 31

What are the outcomes of viral infection?

Answer 31

Fatal, full recovery, permanent damage, persistence